1. Field of the Invention
The present invention relates to new peptides derived from the proinflammatory cytokines Interleukin-1 beta (IL1β) and Tumor Necrosis Factor alpha (TNFα) and their use in human or veterinary therapy. The diseases targeted by these therapeutic uses can be in particular rheumatoid polyarthritis, septic shock, auto-immune diabetes, graft rejection in the host, and also acute or chronic inflammatory diseases, and more generally, diseases linked to the overproduction of ILβ or TNFα cytokines.
2. Description of the Related Art
Active anti-cytokine immunization is an active immunotherapy strategy developed since 1990 by Zagury et al. which is based in particular on Patent Application WO 92/22577. This idea was taken up by several scientific teams which have published in international scientific journals, active immunizations against the entire IFNα protein multimerized by treatment with glutaraldehyde (Gringeri et al., JAIDS 1999; 20:358-70), a chimeric TNFα protein consisting of coupling the native TNFα protein with a T epitope of ovalbumin (Dalum at al., Nature Biotechnology, 1999; 17:666-69), against entire IL9 coupled with KLH (Richard et al., PNAS, 2000; 97:767-72) or also chimeric entire IL5 with a T epitope of tetanus toxin (Hertz et al., J. Immunol, 2001; 167:3792-99).
These approaches have confirmed the feasibility of autologous anti-cytokine immunizations, but these few successes obscure the unsuccessful tests described by certain authors: certain cytokines do not allow sufficiently protective and clinically effective antibodies to be obtained, and the same cytokine prepared in a form which is effective in one manner, will not be effective in another (Richard et al., PNAS, 2000; 97:767-72).
In trying to explain this phenomenon, the Applicant has observed that to date all the authors have used entire cytokines (optionally slightly modified), which leads to difficulties in particular at the following levels:                dilution of the immunogenic power of the antigenic determinants of interest        possible genesis of facilitating antibodies in vivo (E response).        possible genesis of autoimmune reaction to the potential T epitopes present in the entire cytokine (autoimmune T reaction).        
This is why the Applicant has previously claimed families of peptides of limited size between 5 and 40 amino acids originating from cytokines and which have an antigenic power making it possible to generate antibodies against the native cytokine (Patent Application PCT/FR03/01120). EP-A-0218531 also described IL1 peptides used for the preparation of antibodies.
Citation of any document herein is not intended as an admission that such document is pertinent prior art, or considered material to the patentability of any claim of the present application. Any statement as to content or a date of any document is based on the information available to applicant at the time of filing and does not constitute an admission as to the correctness of such a statement.